The effect of whole-body vibration on glucose and lipid profiles in type-2 diabetes: a systematic review and pairwise and network meta-analyses of randomized trials

Whole-body vibration (WBV), a training method based on the stimulation of muscle contraction by mechanical vibration generated in a vibrating platform, is claimed to be effective in diabetes management. This meta-analysis evaluated WBV effects against other exercises, placebo, or no intervention in type-2 diabetes. Medline, Scopus, and Web of Science databases were systematically searched through June 2023. Randomized controlled trials reported the effect of WBV on glucose (hemoglobin A1C and fasting blood glucose), and lipid profiles (total cholesterol, triglycerides, high, and low-density lipoprotein) were included. Two researchers independently extracted the characteristics of the studies, participants, WBV intervention and comparisons, and the outcomes from the included articles. The Physiotherapy Evidence Database (PEDro) scale assessed trial quality. In this review, all articles had no high risk of bias according to the PEDro scale, with studies achieving optimal, excellent, and good scores. Network meta-analysis revealed that WBV was effective for reducing hemoglobin A1C when compared with conventional (mean difference: − 1.58%, 95%CrI: − 2.51, − 0.47) and resistance exercise (mean difference: − 1.32%, 95%CrI: − 1.96, − 0.33). WBV had also a desirable but insignificant effect on hemoglobin A1C compared to stretching and balance exercises, placebo, and no intervention. The current pairwise meta-analysis did not show that WBV favors fasting blood glucose and lipids. WBV may have potential advantages for glycemic control in type-2 diabetes. However, uncertainties in the findings remain due to the limited number of studies and their heterogeneity.


Search strategy
Two researchers separately searched PubMed, Scopus, and Web of Science databases through June 7, 2023.The search was performed using the keywords of study design (randomized clinical trial), participants (people with type-2 diabetes), and intervention (whole body vibration) and their synonyms using medical subject heading keywords.All databases were systematically searched simultaneously.The literature search was developed and conducted by M.B. and A.E. Additionally, a team of two reviewers (M.B and F.M) independently screened duplicate titles, abstracts, and full-text articles.In addition, the reference list of articles included in this review and the list of references included in previous similar reviews were manually searched to identify further pertinent studies.The full search strategy used to identify original research articles for inclusion in the current systematic review is detailed in Supplementary Table 1.

Eligibility criteria
After removing duplicate articles in the Endnote 7 software (Thomson Reuters, New York, NY, USA), two researchers separately screened the title, abstract, and, if required, the full text of the searched articles based on the following criteria.The inclusion criteria were: • Type of participants: people with type-2 diabetes • Type of intervention: whole-body vibration • Type of comparison: any exercise, placebo, or no intervention • Outcomes: hemoglobin A1C, fasting blood glucose, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and • Study design: randomized controlled trial.
Articles in which the total WBV intervention duration was less than 6 weeks 14 or had unclear or unreported data unavailable through the corresponding author were excluded from the review.

Quality evaluation of included articles
Two researchers evaluated the quality and risk of bias of articles included in this review using the Physiotherapy Evidence Database (PEDro) scale.This 11-item scale measures the methodological quality of clinical trials in terms of clarity of inclusion criteria, random allocation of samples to groups, concealment of allocation, homogeneity of groups before receiving the intervention, blindness of samples, therapists, and evaluators, having less than 50% of samples dropping out, measurement of at least one key outcome and reporting their point and variability measurement, reporting of between-group statistical comparisons, and intention-to-treat analysis.Accordingly, each article is graded from 0 to 10, and a higher score indicates its higher quality 15 .

Data extraction
Two researchers independently extracted the following information from the included articles: • Characteristics of the participants: sample size and the mean age of the participants • Characteristics of WBV intervention: length of intervention (week) and its frequency (number of sessions per week), intensity, magnitude, and frequency of vibration, and duration of each session • Characteristics of the comparison group: type of intervention of the control group, length (week) and fre- quency (number of sessions per week) of intervention, and duration of each session • Outcomes: times of study outcome evaluation, and mean changes and standard deviations of each outcome, including hemoglobin A1C (as the primary outcome), fasting blood glucose, total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein (as the secondary outcomes) in the intervention and control groups • Characteristics of the study: first author and year of publication.
The mean and standard deviation were calculated using standard Cochrane formulas in the articles that reported the data as standard error, interquartile range, or confidence interval 16 .In articles with unclear or missing information, the corresponding author was requested to provide the data by email.Any disagreements between the researchers in the study's screening, data extracting, or article quality evaluation stages were resolved by agreement through discussion with a third researcher.

Data synthesis and analysis
Data analysis was conducted using Stata software version 17. Pairwise meta-analysis was conducted using a random-effects model to compare WBV with no intervention or placebo on fasting blood glucose, total cholesterol, triglyceride, and high and low-density lipoprotein.The findings were reported as the mean difference with a 95% confidence interval.Network meta-analysis with a random-effects model was used for multiple comparisons between the WBV and any exercise, no intervention, or placebo on hemoglobin A1C.The ranking probability of each intervention from all included studies was reported as the surface under the cumulative curve (SUCRA) values from zero to one.Accordingly, the intervention with a more significant SUCRA value was more effective 17 .Heterogeneity in each pairwise comparison was estimated using the I 2 statistic; values greater than 25% were considered significant heterogeneity between the studies' results 18 .The generalized inconsistency test also assessed network heterogeneity between studies; a significance level greater than 0.05 indicates consistency 19 .Due to the small number of studies included in the analysis, certainty of the evidence for each direct comparison according to standard Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidance was not assessed 20 .We also could not conduct a network meta-analysis for secondary outcomes.

Ethical approval.
Not applicable.

Systematic search and study selection
Supplementary Fig. 1 illustrates the process of literature searches and study selection.The initial systematic search led to the identification of 289 studies (Supplementary Table 1).There were 243 duplicate articles, and 216 did not qualify according to their titles and abstracts.After adding three trials in the manual search of the reference list of included articles, the study was completed with the analysis of ten papers [21][22][23][24][25][26][27][28][29][30] that met our inclusion criteria.

Characteristics of the included trials
A total of 428 participants was examined in ten trials included in the present meta-analysis.These trials were made available from 2007 to 2021.The percentage of male and female subjects was not reported in some studies 25,30 .In one study 27 , the mean age for all groups was over 70 years, whereas participants in other studies tended to be younger than 70 years old.The hemoglobin A1C level of participants in all trials was less than 10.In 9 trials, the intervention group received only WBV [21][22][23][24][25][26][28][29][30] , while one trial delivered WBV combined with balance exercise 27 . Two tials delivered WBV in six weeks 26,27 , two trials in 8 weeks 23,25 , and the others in 12 weeks.Table 1 shows the characteristics of the trials included in this meta-analysis.

Quality of the included trials
Among all the articles included in this review, no study had a high risk of bias based on the PEDro scale (Supplementary Table 2).Accordingly, five studies obtained optimal scores with a low risk of bias 21,24,25,27,28 , two of which were excellent 25,28 , while the others were good 22,23,26,29,30 .

Network meta-analysis: effect of different interventions on hemoglobin A1C
Figure 1 and Table 2 present the comparative effects of different interventions on hemoglobin A1C.The results indicated that WBV was effective for reducing hemoglobin A1C when compared with conventional (mean difference: − 1.58%, 95%CrI: − 2.51, − 0.47) and resistance exercise (mean difference: − 1.32%, 95%CrI: − 1.96, − 0.33).WBV also had a favorable but insignificant effect on hemoglobin A1C compared to stretching and balance exercises, placebo, and no intervention.Aerobic exercise was effective compared to conventional exercise (mean difference: − 1.64%, 95CrI: − 3.03, − 0.03).None of the other interventions were effective in reducing hemoglobin A1C when compared with placebo and no intervention nor with each other.SUCRA values for the effects of different interventions on hemoglobin A1C highlight WBV as the most effective training (Table 3).

Discussion
Type-2 diabetes is one of the most common metabolic diseases and a healthcare concern worldwide.WBV exercise has gained attention recently for its potential benefits in metabolic control and diabetes management.The evidence suggests that WBV can improve insulin sensitivity, glucose metabolism, and cardiovascular health in individuals with diabetes 11 .The purpose of this study was to write a systematic review and meta-analysis of interventions that investigated the effect of WBV on metabolic indices (glucose and lipid profiles) of people with type-2 diabetes.Interestingly, our network meta-analysis showed that compared to other exercise methods Vol:.( 1234567890 WBV is a simple, not time-consuming, and inexpensive method that can be applied consistently by people with diabetes 11 .By affecting glycosylated hemoglobin as the most critical indicator of glycemic control in diabetes 31 , it seems that WBV helps to reduce diabetes complications and care burdens 32 .Some research focuses on WBV's potential effects on muscle activation and suggests that WBV may activate AMP-activated protein kinase (AMPK) in muscle, which is a key regulator of cellular energy metabolism.Activation of AMPK can lead to various metabolic responses in muscle cells 33 .In other words, as a strong stimulus, WBV causes the continuous and rapid lengthening and shortening of the muscle-tendon complex.Consequently, the muscle spindles are discharged and stimulate the activity of the alpha motor neuron through the monosynaptic and polysynaptic pathways, which leads to the muscles' reflex contraction under the tonic vibration reflex.Muscle contraction causes more glucose uptake from the bloodstream to the muscle cells through various mechanisms, such as reducing the resistance of liver and muscle cells to insulin, increasing glucose transportation protein (GLUT-4), increasing the density of muscle capillaries and muscle blood flow, and increasing glucose absorption by muscles 8,9,34 .Repetition of muscle contraction with vibration stimulation may also affect glycemic targets by arousing endocrine responses and regulating the balance between insulin and glucagon hormones 9,34,35 .
The current study noted a significant decrease of 1.58 and 1.32% in glycosylated hemoglobin in WBV intervention compared to conventional and resisted exercise.This promising finding is comparable to improving glycemic control through medication 36 .An increase in the gravitational load imposed on the musculoskeletal system by the vibration stimulus and, consequently, an increase in the muscle power production capacity can    justify this finding 8 .The WBV also had a desirable effect on hemoglobin A1C compared to stretching and balance, exercises, but without significant differences between the intervention and controls.Of course, this lack of significance is likely due to the small number of studies available for analysis and their diversity in terms of the studied population, vibrating platform parameters, and training protocols.On the other hand, different exercise methods have a proven effect on the glycemic control of people with diabetes.Therefore, it is close to the expectation that, like the WBV, they favor reducing glycosylated hemoglobin 5 .
The strange finding of the present meta-analysis was that WBV intervention's reduction effect on glycosylated hemoglobin was insignificant compared to no intervention or placebo.However, we found only one randomized clinical trial that evaluated the effect of WBV against placebo 37 .The placebo effect of the vibrating platform, along with the attendance of the placebo group participants in the care center to receive the intervention and having the positive social support of peers and experts 38 may explain this finding.Previous research emphasized on the development of standardized interventions to consider different parameters related to the vibration platform, such as its amplitude and frequency and the intensity of the exercises 14 .Regarding the heterogeneity of existing interventions, they seem to underestimate the importance of developing and using standardized vibration and training protocols, may have affected the results.
Unlike the previous study 12 , our study's fasting blood glucose and lipid profile analysis did not show significant differences between WBV and other controls.Notably, few studies investigated these parameters in WBV interventions.In agreement with our findings, another meta-analysis reported no effect of exercise on fasting blood glucose in type-2 diabetes 39 .Available evidence has also reported the dose-response relationship between physical exercise and blood lipid changes 40 .Accordingly, small-volume exercises favor changing blood lipids, but significantly changing these parameters depends on the intensity and dose of exercise training.Maybe the exposure time and intervention volume in the studies included in this meta-analysis were insufficient to change these indices significantly.

The strengths of the study
Globally, the current meta-analysis highlights the main clinical benefits of WBV in type-2 diabetes.This research is the first to use network meta-analysis plus pairwise meta-analysis to compare a variety of controls with WBV.In addition to sound quality, the studies included in our analysis had the highest level of evidence, having a randomized clinical trial design.

The limitations and suggestions
The limited number of studies available for analyzing the variables under investigation introduces some uncertainty to our findings.The existing literature has a great variety in vibration parameters, types of exercise, and training duration.Meanwhile, subgroup analysis was not possible to determine which variable contributed the most to HbA1C improvement.Upcoming research should consider poor consistency between training protocols and try to develop and implement standardized interventions with a larger sample size.Recently published guidelines can be used to introduce all the variables that must necessarily be considered in the development, implementation, and scientific reporting of WBV interventions 7 .The suggestion for future research with a larger sample size and standardized protocols is crucial for advancing our understanding and potentially unlocking new treatment options for diabetes management.In order to provide the best effects, upcoming protocols must contemplate various parameters, including optimal dose-response relationships and various vibration characteristics.Moreover, they need to use suitable methods to monitor the possible side effects of WBV.

Conclusion
WBV can beneficially improve the hemoglobin A1C in type-2 diabetes.This exercise method seems to help reduce diabetes complications and its care burden by improving glycemic control.More well-designed future studies are needed to draw definitive conclusions about the effects of whole-body vibration on blood lipids and fasting sugar in those with diabetes.

Figure 1 .
Figure 1.The effect of whole-body vibration on hemoglobin A1C

Table 1 .
Characteristics of randomized clinical trials included in the systematic review and meta-analysis of the effect of whole-body vibration on glucose and lipid profiles in type-2 diabetes IG: Intervention group; CG: control group; BE: Balance exercise; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; WBV: Whole body vibration

Table 2 .
Comparative effect of different interventions on HbA1c in patients with type 2 diabetes (mean difference and 95% credible interval) WBV: Whole-body vibration

Table 3 .
SUCRA values for the effects of types of interventions on HbA1C

Table 4 .
The effects of whole-body vibration against placebo or no intervention on secondary outcomes